Sample handling apparatus



July 6, 1965 E. w. ANTHON 3,193,148

SAMPLE HANDLING APPARATUS Filed July 2, 1962 5 Sheets-Sheet 1 IIIIIIIII'" 1111111111,

FIE--lf ii I IIIIIIIIIIIIIII/IMIMI/IIII? INVEN TOR.

ERIK W ANTI- 0N July 6, 1965 E. w. ANTHON 3,193,148

SAIPLE HANDLING APPARATUS Filed J u ly 2, 1962 v a Sheets-Sheet 2 0s 1 N Q INVENTOR. ERIK W ANT/ 0N Y SWIM ATTORNEYS July 6, 1965 E. w. ANTHON 3,193,148

SAMPLE HANDLING APPARATUS Filed July 2, 1962 3 Sheets-Sheet 5 INVENTOR E R/K W. AN THON FIE 3 SWIM ATTORNEYS United States Patent 3,193,148 1 SAMPLE HANDLING APPARATUS ErikW. Anthon, Kensington, Califi, assignor, by mesne assignments, to Warner-Lambert Pharmaceutical Company, Morris Plains, N .J.

Filed July 2, 1962, Ser. No. 207,119 6 Claims. (Cl. 222-108) The present invention relates to improvements in a sample handling apparatus, and more particularly to a method and apparatus for transferring a measured quantity of sample or like liquid from one position to another.

- In certain types of analytical procedures, large numbers of routine determinations must be carried out. This is particularly true in biochemical, physiological and medical laboratories where materials such as blood, blood serum, tissue serum, urine or other materials are tested and/or analyzed. These tests are particularly suited for automation because the analytical procedures are repeated a large number of times for similar samples. However, certain of the procedural steps required have been somewhat difficult to automate with comparatively simple and reliable equipment capable of providing the necessary. continued accuracy.

One of the problems encountered in automating such analytical procedures is that of accurately measuring and handling liquid samples where a large number of samples are desired to be handled by the same piece of equipment. One of the difiiculties encountered is the required washing of the piece of equipment used so as to prevent contamination by previously handled samples. One way of handling this problem is to provide means for washing the unit between samples, but this generally requires additional equipment. Thus the present invention provides a simpler and more economical solution to this problem by using a system in which the washing requirement is reduced or completely eliminated.

In most analyses, the analyst is provided with an excess amount of sample and the present invention makes use of this excess to clear or clean the sample handling device from contamination by prior samples. Thus in its process form, the invention provides a method for transferring samples where an excess amount of sample is taken into a pipette or similar transferring device, and then an accurately measured portion of the last taken up sample is delivered to a sample receiving container for further analyses.

In this way, the sample first taken into the pipette is used to wash out prior sample and sweep away contaminants. According to the invention, this excess is discharged to waste. The present invention also provides an apparatus capable of carrying out the above mentioned process in a fully automated fashion. The automated equipment is also designed for easily timed control so that it may be incorporated as a module with other pieces of automated analytic equipment so as to provide these procedural steps in combination with other procedural steps required for and apparatus of the character described in which an exceedingly accurate measure of sample can be taken up and dispensed.

3,193,148 Patented July 6, 1965 ice Still another object of the invention is to provide an apparatus for transferring a measured quantity of sample from one position to another which is capable of handling small liquid samples accurately and automatically.

A still further object of the invention is the provision of an apparatus capable of taking up and delivering a measured quantity of sample by utilizing a unique combination of pumps and a valve mechanism whereby the taking up and delivering of liquid may be completely and automatically controlled through the valve operation alone.

Further objects and advantages of my invention will be apparent as the specification progresses and the new and useful features of my automatic sampling apparatus will be fully defined in the claims attached hereto.

The preferred forms of my invention are illustrated in the accompanying drawing forming a part of this description, in which:

FIGURE 1 is a schematic view of an embodiment of the invention illustrating the broad aspect thereof;

FIGURE 2 is a schematic view illustrating in detail a preferred form of the invention; and

FIGURE 3 a schematic view illustrating still another form of the invention.

While I have shown only the preferred forms of my invention, it should be understood that various changes or modifications may be made within the scope of the claims attached hereto without departing from the spirit of the invention.

In its broad form, the invention combines a probe or pipette capable of taking up a measured quantity of liquid sample or the like, in combination with pump means and a valve for controlling the movement of sample in the probe and a drain for carrying away excess sample used to wash out the probe so as to leave the probe clean for the next operation.

Referring to FIGURE 1 in detail, the broad aspect of the invention is illustrated by an apparatus 11 comprising a sample reservoir source container 13 in which the sample is provided at a sample source site 12, a probe or pipette 14 positioned at the sample source site, a pump 16 for moving sample into and out of the probe, a liquid drain 17 and a valve 18 for regulating the fluid flow provided by the pump.

The sample source site 12 is here shown in one of the containers 13, and the containers are carried on a turntable 19 so as to provide movement into and out of operative position with probe 14. Alternatively, other means could be used to move the samples, if desired. As here shown, the probe 14 is also moved in a reciprocating motion along its axis as indicated by arrow 21. In this way, the probe may be moved into position to discharge into a sample receiver 22 at a sample receiving site. These movements may be mechanized by suitable reciprocating mechanical means (not shown), to render the device suitable for automation.

The pump 16 is simiilar to a hypodermic needle type pump, and comprises a barrel 23 and a piston 24 sliding therein. Valve 18 is a two-way valve which provides communicationbetween pump 16 and tube 26 leading to the probe when in one position and which provides communication between pump 16 and tube 27 leading to the drain when in the other position. Thus when valve 18 is positioned as shown in the drawing, movement of piston 24 causes sample to be taken into or forced out of the passages within the probe 14, the barrel 24 and the tube 26.

In operation of the apparatus of FIGURE 1, the probe 14 is positioned at the sample site and valve 18 is positioned to provide communication between the pump and the probe as illustrated in FIGURE 1. Piston 24 isthen drawn downwards to bring an excess amount of sample I in chamber 39.

'29 into a receiving container.

because'air. pressure from an air compressor 52 passes through the valve from line 33 through the 'valve'in pasa V ,7 w, through the probe into the system. 'The sample first drawn into the probe picks up the contaminants from prior samples so that the last drawn sample remains substantially pure.

With the sample thus drawn into the pipette, the'p robe, is moved into the position shown in phantom in FIGURE 1 for discharge at delivery site .22., The delivery-is accomplished by movement of piston 24 a controlled ,dise

tance so as to discharge a fixed quantity of material. Movement may be effected by hand and indicia provided on the pump for showing thevolume delivered. However, it is'preferred to use a mechanical device '(not shown) to provide controlled automatic movement. After the desired quantity of measured sample is delivered, valve 18 is moved to provide communication between the pump 16' and tube 27-which leads tothe drain 17. Piston 24 is then moved further up to dischargea volume of liquid equivalent to the excess sample taken.

sage 53,-and through line 54 to the chamber 37 of pump 31. "-With chamber 37 pressurized, the piston 41 and associated plungers 42 are moved downwardly to cause chambers 38 and 39 to be decreased in volume so that liquid is discharged from each chamber. In this way,

the sample last taken into theprobe or pipette is discharged into-a container at a delivery site with the amount f sample so delivered positively determined bythe'reduc- ,tion in volume of 'chamber'39; At the same time excess sample in chamber 38' is discharged through line 56, passage 57, and line 58 to drain 59.

After clean sample and waste sample are delivered. as explained above,.valveelement 51 is positioned to provide its passages in'the position shown in, phantom, by any suitable means. As here shown, the element is moved by reciprocating 'member 61 ,which'is operated by-an eccentric'6tl through amoto'r (not shown) which is activated' by suitable relays (not shown) in order to-bring curately measured quantity of sample from one position 6 to another. As-here shown, the apparatus. comprises a probe or pipette 29, pump 31, and a valve 32 which pro-:

vides communication between the pump and either pressure line 33 or vacuum line 34.

'Pump 31 is adapted toope'rateby means of sure or vacuum with the air pressure causing thev pump to move in one directionand the vacuum causing it to move in reverse direction. 1 Thus the pump comprises a housing 36 enclosing chambers 37, 38 and 39.with chamber 37 adapted to contain air under pressure or vacuum on one side of a piston 41 with the'other side vented; Piston air pres.-

41 is carried on a special plunger 42 which reciprocates in both chamber 38 and 39 and is sealed through the: housing to prevent fluid communicationbetween the chambers.

As shown in'FIGURE 2, plunger'42 has a shoulder 43 reciprocating in chamber 38, and an end 44'reciprocating Thus plunger 42 simultaneously adjusts the volume in bothchambers'38 and 39 and effects moven ment of liquids into and out of each chamber depending upon the valve positions. 7 q In order to accurately adjust the volume of liquid taken into'the-chambers 3Sand 39, stop means 46 is provided to limit the movementof the piston 41. In order I to adjust the stop means 46, knurled handle47 is rotated.

so as to move stop' means 46 through its sealed threaded engagement with the housing 36.: The setting may be accurately adjusted on a suitable gage 48 which-may-in- 'clude a Vernier scale (not shown) orany other conventional measuring scale for providing accurate measurements.

The valve 32 may be any valve structure capable of providing the communications shown for .theLp'osition' illustrated in the drawing and the position shown in phantom in the drawing While I have shown the schematic representation for valve 32,"a suitable valvemay be con structed in which valve elements from one position to the other. A 'preferred' valve and,

49-and 51 are slidable mechanism for operating the same is described and claimed in the copending application Serial No. 183,506,

filed March 29, 1962, entitled Valve, of Erik W. Anthon, the inventor in the present application.

In operation, 'the device. has the valve position shown when liquid is-being discharged from the' probe or'pi-pette This discharge is efiected incompressable liquids.

the valveoperation in proper. timed relation with any other components that may be added to carry out other analytical process steps. l I .Thus when the valve is positioned at the oppoisteextreme the passages 53, '57 and 62 are raised as shown inphantom on thedr'awing; andthe chamber 37 of the pump 31fisconnected to the suctionsidejof the pump through'loop passage ,62 in the'valve and :line 34. With this connection; the plunger 42; is drawn upwardly and,

the chambers 38 and 39 are increased in volume so. as to suck in fluid and fill the chambers withsample; both chambers being in communication .with each other 'through'line 63, passage 57 andline 64.

. It is important-"in the, operation of this-mechanism. that thechambers andassociatedlines be kept filled .Withliquid atall times: so that the pump operates; accurately through The timing is arranged so that suificient time is allowed. for the'liquids-to' be drawn inthe chambers with the plunger moved to the full position possible in contact with the associated "stop means 47. In

thisway, ran volumes of liquid'are taken up and de- The probe 29 may be moved from thesample site to the delivery site by any suitable mechanism such as the Materials Handling Apparatusrdescribed and claimed in the United States patent application Serial No.,61,206 filed October 7; 1960 by Erik W. Anthon, the inventor in the present application." Alternatively, the samples may'befmoved with'resp'ect to the probe as shown in FIGURE; 1.

In the embodiment of FIGURE 2, theuratio of excess r sample usedto wash the probe or. pipette to the measured sample transferred is a constant determined by the ratio of the cross-sectional area of the annular space in chamber 38 to the cross-sectional area of the plunger. in chamber 39. However, itis desirable to provide a mechanism in which the ratio may be adjusted so that a large excess is used when available while a'small excess is used when the sample is limited. Such a device is shown in the embodiment of FIGURE 3.

As there shown, the devicecomprises a probe 29, valve 32, drain 59, air-compressor 52, and associated connecting lines all similar to'the embodiment of'FIGURE 2. However, the embodime'ntof-FIGURE 3' has two separate 7 pumps 66 and 67 instea drofpurnp 31. Pump66 takes up the excess-sample and discharges it to the drain, while pump 67 draws in: andldischarges the sample used for analysis. "Separatejadjustments are provided on each pump to provide the desired ratio. of' excess sample to the sample used.

Both pumps 66 and 67 are similarly constructedand adapted to operate by "means. of air pressure or vacuum with'the air? pressure causing the pumps to move in, one direction and the vacuum causing them '.to; move in reverse direction; Thus each-pump comprises a housing 68 enclosing chambers 69 and-71'with chambers 69 adapted to activea piston 72 which has a plunger 73 that communicates down into chamber 71 and effects movement of liquid into and out of the chamber depending upon the valve positions in the associated lines.

In order to accurately adjust the volume of liquid taken into the chambers 69, stop means 74 are provided to limit the movement of the piston 72. In order to adjust the stop means 74, knurled handle 76 is rotated to move stop means 74 axially through the threaded engagement in the housing 68 as shown in FIGURE 3. The adjustment may be accurately controlled by means of a suitable gage 77 which may include a vernier scale (not shown) or any other conventional measuring scale for providing accurate measurements.

In operation, the device is moved to the position shown when liquid is being discharged from the probe or pipette 29 into the receiving container 13. This discharge is eflected because air pressure enters from air pressure source 52 and communicates through lines 33, 78 and 79 to the chambers 69 to force the pistons 72 downwardly. This causes chambers 71 to be decreased in volume so that liquid from the upper chamber 71 goes through lines 56 and 58 to drain 59, while the liquid in the lower chamber 71 goes through line 81 and out of the probe 29. The probe and/or sample containers are then moved for transferring the next sample.

With the probe 29 in position for receiving the next sample, valve 32 is operated to move the passages 53, 57 and 62 to the position shown in phantom in the drawing. Chambers 69 are then in communication with the suction side of the air compressor so as to be provided with a vacuum. This vacuum causes plungers 73 to move upwards and draw sample into the pipette with the amount of excess sample being determined by the volume of chamber 71 of pump 66 and the amount of measured sample to be used determined by the volume of chamber 71 of pump 67. The probe is then positioned for delivery of the sample as mentioned above.

From the foregoing description, it is seen that I have provided a method and apparatus for transferring and measuring a fixed quantity of sample by a device suitable for automation, in which the parts of the device in contact with the sample are cleaned by the sample being transferred.

I claim:

1. An apparatus for transferring a measured quantity of sample from one position to another, comprising a sample reservoir source container at a sample source site where a sample is provided, a probe for taking up sample, a sample receiver at a sample receiving site where sample is to be delivered from the probe, a drain for receiving excess sample, a first pump means for drawing up a measured quantity of sample into said probe when the probe is in position at the sample site, a second pump for taking up a measured quantity of excess sample into the probe, said excess sample being present in an amount sufficient to clean the probe so as to prevent contamination by prior samples, and valve means for connecting said first and second pump means to the probe when the pump means are taking up sample and for connecting said first pump means to the probe for delivery of sample at the sample receiving site while connecting said second pump means to the drain for expulsion of excess sample.

2. The apparatus defined in claim 1, in which said first pump means and said second pump means are operated by air pressure and a vacuum from an air compressor, with said valve connecting the pump means to the pressure side for one stroke and to the vacuum side for the reverse stroke.

3. The apparatus defined in claim 2, in which stop means are provided for adjusting the length of the stroke of the pump and a gage is included to indicate the amount of sample being taken up by the probe.

4. An apparatus for transferring a measured quantity of sample from one position to another, comprising a sample reservoir source container at a sample source site where a sample is provided, a probe for taking up sample, a sample receiver at a sample receiving site where sample is to be delivered from the probe, a drain for carrying away excess sample, a pump having a cylinder with three separate and distinct chambers and a plunger in communication with said chambers, one of said chambers being utilized to take up sample on one stroke of the piston and to distribute sample from each of the chambers on the opposite stroke of the piston, and a valve for simultaneously adjusting the pressure in said chamber used to reciprocate the plunger while providing fluid communication between the other two of said chambers and the probe as the sample is taken up and providing fluid communication with one of said other two chambers with the probe while sample is being discharged and the other of said other two chambers with the drain as the sample is being discharged.

5. An apparatus for transferring a measured quantity of sample from one position to another, comprising a reservoir source container in which sample is provided at a sample source site, a probe for taking up and discharging sample, a sample receiver at a sample receiving site where sample is to be received from the probe, a drain for receiving excess sample, a fluid conduit extending between the probe and the drain, said probe being in the form of a hollow tube having an opening at one end for taking in and discharging sample and another opening for attachment to the fluid conduit, pump means in fluid communication to the conduit for drawing up sample in an amount suflicient to provide an excess of sample capable of cleaning the probe together with a measured quantity of sample and for delivering the measured quantity of sample to the receiver and the excess of sample to the drain, and a two-position valve means for directing the fluid movement through the probe and fluid conduit as it is pumped whereby in one position fluid communication between the pump means and the drain is closed and fluid communication between the pump means and the probe is open and, in the other position, the fluid communication between the pump means and drain is open and fluid communication between the pump means and probe is closed.

6. An apparatus for transferring a measured quantity of sample from one container to another, comprising a reservoir source container in which sample is provided at a sample source site, a probe for taking up and discharging sample, a sample receiver at a sample receiving site where sample is to be received from the probe, a drain for receiving excess sample, a fluid conduit extending between the probe and the drain, said probe being in the form of a hollow tube having an opening at one end for taking in and discharging sample and another opening for attachment to the fluid conduit, a branch conduit connected with the fluid conduit at a junction, a pump in the branch conduit for bringing fluid into and moving fluid out of the branch conduit, and a two-position valve at the junction of the branch conduit and fluid conduit for establishing fluid communication between the pump and the probe while shutting off fluid communication to the drain in one position and for establishing fluid communication to the drain while shutting oif fluid communication to the probe in another position.

References Cited by the Examiner UNITED STATES PATENTS 333,140 12/85 Longley 222-409 1,736,392 11/29 COSs et al. 141-27 2,624,656 1/53 Andrews et al 23-259 2,966,175 12/60 Hyde 141-27 3,067,915 12/62 Shapiro et al. 222-255 EVERETT W. KIRBY, Primary Examiner.

LOUIS I. DEMBO, Examiner.

Dedication 3,193,148.-Erik W. Anthon, Kensington, Calif. SAMPLE HANDLING AP- PARATUS. Patent dated July 6, 1965. Dedication filed Mar. 2, 1970, by the assignee,Aww1"ican Optical Corporation. Hereby dedicates the remaining term of said patent to the Public.

[Ofioial Gazette July 7, 1.970.] 

1. AN APPARATUS FOR TRANSFERRING A MEASURED QUANTITY OF SAMPLE FROM ONE POSITION TO ANOTHER, COMPRISING A SAMPLE RESERVOIR SOURCE CONTAINER AT A SAMPLE SOURCE SITE WHERE A SAMPLE IS PROVIDED, A PROBE FOR TAKING UP SAMPLE, A SAMPLE RECEIVER AT A SAMPLE RECEIVING SITE WHERE SAMPLE IS TO BE DELIVERED FROM THEPROBE, A DRAIN FOR RECIEVING EXCESS SAMPLE, A FIRST PUMP MEANS FOR DRAWING UP A MEASURED QUANTITY OF SAMPLE INTO SAID PROBE WHEN THE PROBE IS IN POSITION AT THE SAMPLE SITE, A SECOND PUMP FOR TAKING UP A MEASURED QUANTITY OF EXCESS SAMPLE INTO THE PROBE, SAID EXCESS SAMPLE BEING PRESENT IN AN AMOUNT SUFFICIENT TO CLEAN THE PROBE SO AS TO PREVENT CONTAMINATION BY PRIOR SAMPLES, AND VALVE MEANS FOR CONNECTING SAID FIRST AND SECOND PUMP MEANS TO THE PROBE WHEN THE PUMP MEANS ARE TAKING UP SAMPLE AND FOR CONNECTING SAID FIRST PUMP MEANS TO THE PROBE FOR DELIVERY OF SAMPLE AT THE SAMPLE RECEIVING SITE WHILE CONNECTING SAID SECOND PUMP MEANS TO THE DRAIN FOR EXPULSION OF EXCESS SAMPLE. 